Early colonizing Escherichia coli elicits remodeling of rat colonic epithelium shifting toward a new homeostatic state

We investigated the effects of early colonizing bacteria on the colonic epithelium. We isolated dominant bacteria, Escherichia coli, Enterococcus faecalis, Lactobacillus intestinalis, Clostridium innocuum and a novel Fusobacterium spp., from the intestinal contents of conventional suckling rats and transferred them in different combinations into germfree (GF) adult rats. Animals were investigated after various times up to 21 days. Proliferative cell markers (Ki67, proliferating cell nuclear antigen, phospho-histone H3, cyclin A) were higher in rats monocolonized with E. coli than in GF at all time points, but not in rats monocolonized with E. faecalis. The mucin content of goblet cells declined shortly after E. coli administration whereas the mucus layer doubled in thickness. Fluorescence in situ hybridization analyses revealed that E. coli resides in this mucus layer. The epithelial mucin content progressively returned to baseline, following an increase in KLF4 and in the cell cycle arrest-related proteins p21^CIP1 and p27^KIP1. Markers of colonic differentiated cells involved in electrolyte (carbonic anhydrase II and slc26A3) and water (aquaglyceroporin3 (aqp3)) transport, and secretory responses to carbachol were modulated after E. coli inoculation suggesting that ion transport dynamics were also affected. The colonic responses to simplified microbiotas differed substantially according to whether or not E. coli was combined with the other four bacteria. Thus, proliferation markers increased substantially when E. coli was in the mix, but very much less when it was absent. This work demonstrates that a pioneer strain of E. coli elicits sequential epithelial remodeling affecting the structure, mucus layer and ionic movements and suggests this can result in a microbiota-compliant state.     

Time is money. Waiting costs explain why selection favors steeper time discounting in deprived environments

Individuals exposed to deprivation tend to show a characteristic behavioral syndrome suggestive of a short time horizon. This pattern has traditionally been attributed to the intrinsically higher unpredictability of deprived environments, which renders waiting for long term rewards more risky (i.e. collection risks are high). In the current paper, based on a simple dynamic life history model, we show that a significant portion of individuals' propensity to discount future rewards might have a completely distinct origin. Upon collecting a resource, individuals have the opportunity to accumulate “capital” (e.g. grow muscular tissue, build a protective shelter, buy a car, etc.), which eventually increases their productivity and/or their chances of survival. As a result, delaying the collection of a resource creates an opportunity cost in the sense that during the waiting time, the benefits otherwise generated by the increment in capital are lost. These forgone benefits are independent of collection risks and constitute waiting costs per se. Using optimal control theory we show that these costs can lead to the evolution of short time horizons even in the complete absence of collection risks. Moreover, assuming diminishing returns to capital, we show that the evolutionarily stable time horizon increases with the amount of capital already owned by individuals. When individuals possess little capital, they have a lot of room to improve their productivity and/or survival, hence they should be impatient to collect resources; that is, their time horizon should be short. On the contrary, when individuals already possess a lot of capital, the benefits of further accumulation are plateauing, hence patience becomes a more profitable strategy and individuals should lengthen their time horizon. This means that individuals get more patient as they age and that people in deprivation, who still have important productive and survival needs that can be satisfied, should have a shorter time horizon. This result leads us to interpret the behavioral constellation of deprivation in a new way.     

Intracellular pH control in Dictyostelium discoideum: A P-NMR analysis

Phosphorus metabolites and intracellular pH have been examined in the slime mold Dictyostelium discoideum by non-destructive ³¹P-NMR measurements. In a spectrum from a suspension of aerobic amoebae, the major peaks are inorganic phosphate, nucleotide di- and triphosphates. In the corresponding perchloric acid extract, resonances originating from purine and pyrimidine nucleotides are resolved. Adenine nucleotides are the most abundant components, but the other nucleotides are present in significant amounts. In a spectrum from intact spores in a dormant state, only inorganic phosphate and polyphosphates are detected and nucleotides are no longer present in large amounts.Of particular importance is the ability to observe separately in aerobic amoebae the resonance of inorganic phosphate localized in two different cell compartments: the cytosol and the mitochondria. The cytosolic pH and mitochondrial pH have been measured as 6.7 and 7.7, respectively, on the basis of intracellular inorganic phosphate chemical shifts. They are essentially unaffected over a large range of external pH and they are not modified transiently or permanently during the initiation of the developmental program of the organism. A weak acid, such as propionate, which modifies the progression of differentiation by favoring prestalk cells, perturbs intracellular pH gradients by selectively decreasing mitochondrial pH without any effect on cytosolic pH.     

Cytosolic acidification as a signal mediating hyperosmotic stress responses in Dictyostelium discoideum

Background  

Dictyostelium cells exhibit an unusual response to hyperosmolarity that is distinct from the response in other organisms investigated: instead of accumulating compatible osmolytes as it has been described for a wide range of organisms, Dictyostelium cells rearrange their cytoskeleton and thereby build up a rigid network which is believed to constitute the major osmoprotective mechanism in this organism. To gain more insight into the osmoregulation of this amoeba, we investigated physiological processes affected under hyperosmotic conditions in Dictyostelium.     

G-quadruplexes and helicases

Guanine-rich DNA strands can fold in vitro into non-canonical DNA structures called G-quadruplexes. These structures may be very stable under physiological conditions. Evidence suggests that G-quadruplex structures may act as ‘knots’ within genomic DNA, and it has been hypothesized that proteins may have evolved to remove these structures. The first indication of how G-quadruplex structures could be unfolded enzymatically came in the late 1990s with reports that some well-known duplex DNA helicases resolved these structures in vitro. Since then, the number of studies reporting G-quadruplex DNA unfolding by helicase enzymes has rapidly increased. The present review aims to present a general overview of the helicase/G-quadruplex field.